RPP21

Chr 6

ribonuclease P subunit p21

Also known as: C6orf135, CAT60

NCBI Gene: 79897ENSG00000241370UniProt: Q9H633

RPP21 is a protein subunit of nuclear ribonuclease P, which processes the 5-prime leader sequence of precursor tRNAs (Jarrous et al., 2001 [PubMed 11497433]).[supplied by OMIM, Jan 2009]

16
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RPP21
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 8 VUS of 16 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.59LOEUF
pLI 0.000
Z-score 0.35
OE 0.87 (0.49–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.29Z-score
OE missense 0.92 (0.77–1.09)
88 obs / 95.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.87 (0.49–1.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.77–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 7 / 8.1Missense obs/exp: 88 / 95.9Syn Z: -1.05

ClinVar Variant Classifications

16 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS8
Likely Benign2
5
Pathogenic
1
Likely Pathogenic
8
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
8
0
0
8
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0106016

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RPP21 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.
Kunz M et al.·Exp Dermatol
2015
Sofosbuvir induces gene expression for promoting cell proliferation and migration of hepatocellular carcinoma cells.
Tsai WL et al.·Aging (Albany NY)
2022
RNase P protein subunit Rpp29 represses histone H3.3 nucleosome deposition.
Newhart A et al.·Mol Biol Cell
2016
cGMP-dependent protein kinase I interacts with TRIM39R, a novel Rpp21 domain-containing TRIM protein.
Roberts JD Jr et al.·Am J Physiol Lung Cell Mol Physiol
2007
Comprehensive analysis reveals common DNA methylation patterns of tobacco-associated cancers: A pan-cancer analysis.
Liu X et al.·Gene
2021
Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci.
Ning L et al.·Commun Biol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Sequence Variant in the TRIM39-RPP21 Gene Readthrough is Shared Across a Cohort of Arabian Foals Diagnosed with Juvenile Idiopathic Epilepsy.
Polani S et al.·J Genet Mutat Disord
2022Cohort
TRIM39-RPP21 Variants (∆19InsCCC) Are Not Associated with Juvenile Idiopathic Epilepsy in Egyptian Arabian Horses.
Rivas VN et al.·Genes (Basel)
2019🔓 Open Access
A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks.
Abu-Zhayia ER et al.·Sci Rep
2017🔓 Open Access
Functional characterization of archaeal homologs of human nuclear RNase P proteins Rpp21 and Rpp29 provides insights into the molecular basis of their cooperativity in catalysis.
Jiang D et al.·Biochem Biophys Res Commun
2017Functional
Thermodynamics of coupled folding in the interaction of archaeal RNase P proteins RPP21 and RPP29.
Xu Y et al.·Biochemistry
2012
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools